Comparison of the yield of two tuberculosis screening approaches among household contacts in a community setting of Silti Zone, Central Ethiopia: a prospective cohort study.

BACKGROUND: Household contacts of tuberculosis (TB) patients are at a greater risk of infection and developing TB as well. Despite recommendations to actively screen such high-risk groups for TB, it is poorly implemented in Ethiopia. A community-based household contact screening was conducted to compare the yield of two different screening approaches and to identify factors associated with TB occurrence. METHODS: Smear-positive pulmonary TB index cases from six health facilities in six districts of Silti Zone were identified and enrolled prospectively between September 2020 and December 2022. Trained healthcare workers conducted house visits to screen household contacts for TB. WHO (World Health Organization) recommended symptom-based screening algorithms were used. The yield of screening was compared between a two-time screening at study site I and a single baseline screening at study site II, which is the current programmatic approach. Generalized estimating equation was used to run multivariate logistic regression to identify factors associated with TB occurrence. RESULTS: A total of 387 index TB cases (193 at site I and 194 at site II) with 1,276 eligible contacts were included for analysis. The TB yield of repeat screening approach did not show a significant difference compared to a single screening (2.3% at site I vs. 1.1% at site II, p < 0.072). The number needed to screen was 44 and 87 for the repeat and single screening, respectively, indicating a high TB burden in both settings. The screening algorithm for patients with comorbidities of asthma and heart failure had a 100% sensitivity, 19.1% specificity and a positive predictive value of 5.6%. Cough [AOR: 10.9, 95%CI: 2.55,46.37], fatigue [AOR: 6.1, 95%CI: 1.76,21.29], daily duration of contact with index case [AOR: 4.6, 95%CI; 1.57,13.43] and age of index cases [AOR: 0.9, 95%CI; 0.91-0.99] were associated with the occurrence of TB among household contacts. CONCLUSION: Our study showed that the yield of TB was not significantly different between one-time screening and repeat screening. Although repeat screening has made an addition to case notification, it should be practiced only if resources permit. Cough, fatigue, duration of contact and age of index cases were factors associated with TB. Further studies are needed to establish the association between older age and the risk of transmitting TB.

Hierarchical Predictors of Mortality in Neonatal Sepsis at Jimma Medical Center, Ethiopia: A Case-Control Study.

Background: Neonatal sepsis made the neonatal period the most perilous time for child survival, and it continued to cause preventable mortalities worldwide. These mortalities stem from the interaction of several factors that have not been sufficiently studied and, in some cases, remain overlooked. Thus, the study aims to investigate the predictors of mortality that arise from the interaction of these factors and quantitatively determine their etiologic fraction. Methods: A case-control study with hierarchical data input was conducted at Jimma Medical Center (JMC) in Oromia, Ethiopia, spanning from May 2022 to July 2023. It employed logistic regression to calculate adjusted odds ratios (AORs) and their corresponding 95% confidence intervals (CI) at a significance level of p ≤ 0.05. The model adjusted odds ratios (ORs) for variables within each level and farther levels and presented an etiologic fraction (EF), indicating the proportion of neonatal mortality attributable to specific factors. Results: The analysis of 67 cases and 268 controls unveiled significant predictors of mortality in sepsis that emerged from distal, intermediate, and proximal levels. In the final model, thus, rural residence [AOR 3.1; 95% CI (1.5, 6.3), p ≤ 0.01], prolonged labor [AOR 4.5; 95% CI (2.2, 9.3), p ≤ 0.01], prematurity [AOR 3.9; 95% CI (1.9, 7.9), P ≤ 0.0], gram-negative bacteremia [AOR 3.8; 95% CI (1.9, 7.6); P ≤ 0.01], convulsion [AOR 3.2; 95% CI (1.6, 6.4); P ≤ 0.03], low birth weight [AOR 2.7; 95% CI (1.3, 5.4); P≤0.01], and delayed breastfeeding [AOR 2.5; 95% CI (1.2, 4.9); P ≤ 0.01] attributed a variable percentage of mortality. Conclusion: Factors emerging and interacting at distal (residence), intermediate (prolonged labor), and proximal (prematurity, birth weight, convulsion, bacterial etiology, and feeding) levels influence neonatal mortality in sepsis at JMC. Therefore, concurrently improving rural family characteristics, managing labor duration, strengthening diagnostic stewardship, and promoting essential newborn care can actively prevent and reduce these mortalities.

Resistance to pyrazinamide in Mycobacterium tuberculosis complex isolates from previously treated tuberculosis cases in Southwestern Oromia, Ethiopia.

Objective: Pyrazinamide (PZA) susceptibility testing is important to develop evidence-based algorithms for case management. We aimed to assess the prevalence of PZA-resistance and its impact on treatment outcomes in previously treated tuberculosis (TB) cases in southwestern Oromia, Ethiopia. Methods: A Phenotypic Drug Susceptibility Testing (DST) of PZA with BACTEC MGIT 960 was conducted at the Mycobacteriology Research Center of Jimma University (MRC-JU) from June to November 2021 on sixty-six Mycobacterium tuberculosis complex (MTBC) isolates from previously treated TB cases. SPSS software package version 21 was used. The differences in the proportion of PZA resistance between the groups were compared using the chi squared test. Logistic regression was used to identify the association between PZA resistance and treatment outcomes. Results: Among 66 MTBC isolates (49 rifampicin-resistant and 17 rifampicin-sensitive) included in this study, 31.8 % were resistant to PZA. The proportion of PZA resistance was almost three times higher in previously treated TB cases with rifampicin resistance than in rifampicin-sensitive patients (38.8 % vs. 11.8 %, p = 0.039). An unfavorable treatment outcome was documented for 23 % (15/65) of the participants. Patients with PZA resistance were almost four times more likely to have an unfavorable treatment outcome than patients with PZA sensitive (aOR 4.2, 95 % CI: 1.13-15.3). Conclusions: The prevalence of PZA resistance was high compared to the pooled PZA resistance estimated worldwide. The majority of TB cases with PZA resistance had an unfavorable treatment outcome. PZA susceptibility testing should be included in the multidrug-resistant TB diagnostic algorithm to improve management of these patients.

Discordance between genotypic and phenotypic methods for the detection of rifampicin and isoniazid resistant Mycobacterium tuberculosis and the correlation with patient treatment outcomes.

Background: Accurate drug susceptibility testing (DST) of Mycobacterium tuberculosis (MTB) is essential for proper patient management. We investigated discordance between genotypic (Xpert MTB/RIF and MTBDRplus) and phenotypic (MGIT 960) methods for the detection of rifampicin (RIF) and isoniazid (INH) resistant MTB and its correlation with patient treatment outcomes in Jimma, Southwest Oromia, Ethiopia. Methods: A retrospective study was conducted on 57 stored MTB isolates with known Xpert RIF resistance status (45 RIF resistant and 12 RIF susceptible) at Jimma University Mycobacteriology Research Center from November 2, 2021, to December 28, 2022. We did MTBDRplus and phenotypic DST (using the Mycobacterial Growth Indicator Tube (MGIT) system). The Xpert and MTBDRplus results were compared using phenotypic DST as a reference standard method. The treatment outcome was determined as per national guideline. The discordance between the genotypic and phenotypic DST was calculated using GraphPad software. Results: Among the 57 MTB isolates, six (10.5 %) had discordant results between the two DST methods. Xpert yielded five discordant results for RIF when compared with phenotypic DST (kappa coefficient (κ) = 0.76, 95 % confidence interval 0.56-0.96). The MTBDRplus compared with phenotypic DST gave three discordant results for RIF (κ = 0.86, 95 % confidence interval 0.71-1.00) and three for INH (κ = 0.86, 95 % confidence interval 0.70-1.00). Compared with Xpert, MTBDRplus yielded lower discordance with phenotypic DST for RIF. Out of six patients with discordant results, three had unfavorable outcomes while the other three were cured. Of the three patients with unfavorable outcomes, only one patient has received an inappropriate treatment regimen. There was no correlation between unfavorable outcomes and incorrect treatment regimens due to discordant results (Χ2 = 0.404; P = 0.525). Conclusions: Discordance between genotypic and phenotypic DST for RIF or INH occurred in 10.5 % of isolates. Only one patient with discordant results has received an inappropriate treatment regimen, resulting in an unfavorable outcome. The impact of parallel use of rapid molecular assay with phenotypic DST on patient treatment outcomes requires further study.

Bacterial pathogens in Xpert MTB/RIF Ultra-negative sputum samples of patients with presumptive tuberculosis in a high TB burden setting: a 16S rRNA analysis.

In patients with presumptive tuberculosis (TB) in whom the diagnosis of TB was excluded, understanding the bacterial etiology of lower respiratory tract infections (LRTIs) is important for optimal patient management. A secondary analysis was performed on a cohort of 250 hospitalized patients with symptoms of TB. Bacterial DNA was extracted from sputum samples for Illumina 16S rRNA sequencing to identify bacterial species based on amplicon sequence variant level. The bacterial pathogen most likely to be responsible for the patients' LRTI could only be identified in a minority (6.0%, 13/215) of cases based on 16S rRNA amplicon sequencing: Mycoplasma pneumoniae (n = 7), Bordetella pertussis (n = 2), Acinetobacter baumanii (n = 2), and Pseudomonas aeruginosa (n = 2). Other putative pathogens were present in similar proportions of Xpert Ultra-positive and Xpert Ultra-negative sputum samples. The presence of Streptococcus (pseudo)pneumoniae appeared to increase the odds of radiological abnormalities (aOR 2.5, 95% CI 1.12-6.16) and the presence of S. (pseudo)pneumoniae (aOR 5.31, 95% CI 1.29-26.6) and Moraxella catarrhalis/nonliquefaciens (aOR 12.1, 95% CI 2.67-72.8) increased the odds of 6-month mortality, suggesting that these pathogens might have clinical relevance. M. pneumoniae, B. pertussis, and A. baumanii appeared to be the possible causes of TB-like symptoms. S. (pseudo)pneumoniae and M. catarrhalis/nonliquefaciens also appeared of clinical relevance based on 16S rRNA amplicon sequencing. Further research using tools with higher discriminatory power than 16S rRNA sequencing is required to develop optimal diagnostic and treatment strategies for this population.IMPORTANCEThe objective of this study was to identify possible bacterial lower respiratory tract infection (LRTI) pathogens in hospitalized patients who were initially suspected to have TB but later tested negative using the Xpert Ultra test. Although 16S rRNA was able to identify some less common or difficult-to-culture pathogens such as Mycoplasma pneumoniae and Bordetella pertussis, one of the main findings of the study is that, in contrast to what we had hypothesized, 16S rRNA is not a method that can be used to assist in the management of patients with presumptive TB having a negative Xpert Ultra test. Even though this could be considered a negative finding, we believe it is an important finding to report as it highlights the need for further research using different approaches.

Genomic transmission clusters and circulating lineages of Mycobacterium tuberculosis among refugees residing in refugee camps in Ethiopia.

BACKGROUND: Understanding the transmission dynamics of Mycobacterium tuberculosis (Mtb) could benefit the design of tuberculosis (TB) prevention and control strategies for refugee populations. Whole Genome Sequencing (WGS) has not yet been used to document the Mtb transmission dynamics among refugees in Ethiopia. We applied WGS to accurately identify transmission clusters and Mtb lineages among TB cases in refugee camps in Ethiopia. METHOD AND DESIGN: We conducted a cross-sectional study of 610 refugees in refugee camps in Ethiopia presenting with symptoms of TB. WGS data of 67 isolates was analyzed using the Maximum Accessible Genome for Mtb Analysis (MAGMA) pipeline; iTol and FigTree were used to visualize phylogenetic trees, lineages, and the presence of transmission clusters. RESULTS: Mtb culture-positive refugees originated from South Sudan (52/67, 77.6%), Somalia (9/67, 13.4%). Eritrea (4/67, 6%), and Sudan (2/67, 3%). The majority (52, 77.6%) of the isolates belonged to Mtb lineage (L) 3, and one L9 was identified from a Somalian refugee. The vast majority (82%) of the isolates were pan-susceptible Mtb, and none were multi-drug-resistant (MDR)-TB. Based on the 5-single nucleotide polymorphisms cutoff, we identified eight potential transmission clusters containing 23.9% of the isolates. Contact investigation confirmed epidemiological links with either family or social interaction within the refugee camps or with neighboring refugee camps. CONCLUSION: Four lineages (L1, L3, L4, and L9) were identified, with the majority of strains being L3, reflecting the Mtb L3 dominance in South Sudan, where the majority of refugees originated from. Recent transmission among refugees was relatively low (24%), likely due to the short study period. The improved understanding of the Mtb transmission dynamics using WGS in refugee camps could assist in designing effective TB control programs for refugees.

Epidemiologic features of neonatal sepsis and its COVID-19 associated temporal patterns in Jimma Medical Center, Ethiopia: A Joinpoint regression analysis.

BACKGROUND: Neonatal sepsis remains a leading cause of morbidity and mortality in neonates across all regions, including Africa. Compared to developed and some developing countries, there are relatively few epidemiological trends for neonatal sepsis and associated patterns with COVID-19 in Ethiopia. We modeled an epidemiological trend and pattern to aid in the monitoring of changes in neonatal sepsis. METHODS: Retrospective data were collected from all admissions to the Neonatal Intensive Care Unit (NICU) in Ethiopia at Jimma Medical Center between May 2019 and April 2022. We analyzed the monthly neonatal sepsis incidence, mortality, and case-fatality rates using STATA software. Finally, we modeled a monthly time series of neonatal sepsis incidence trends and patterns associated with the COVID-19-impacted period using Joinpoint software. For all analyses, a P value of 0.05 was considered statistically significant at the 95% confidence interval (CI). RESULTS: In the 36 months, 6796 cases were admitted to the NICU, with a 9.5% (95% CI: 9.1, 10.0) incidence rate of neonatal sepsis. The overall admission mortality rate was 16.5% (95% CI: 13.6, 19.8), while sepsis-attributed mortality was 7.1% (95% CI: 5.8, 8.5). The data showed an unstable decreasing trend for three Joinpoints (August 2020, December 2020, and August 2021). Notably, a decrease in the incidence trend was observed from May 2019 to August 2020 (MPC, -4.1; 95% CI: -7.6, -0.5; P = 0.03), followed by a sharp increase (MPC, 23.7; 95% CI: -13.8, 77.7; P = 0.24) from August 2020 to December 2020. From December 2020 to August 2021, there was again a decreasing trend (MPC, -13.8; 95% CI: -23.3, -3.5; P = 0.01), followed by a slight increase from August 2021 to April 2022 (MPC, 4.2; 95% CI: -8.4, 18.6; P = 0.52). Finally, the study revealed an association between patterns of neonatal sepsis incidence trends and COVID-19, with a Joinpoint jump model comparability ratio (CR = 0.43) between pre- and COVID-19-impacted periods. CONCLUSIONS: Neonatal sepsis was prevalent at Jimma Medical Center, but it was on an unstably declining trend. The current results suggest a potential temporal association between the intensity of COVID-19 containment measures and a change in the incidence trend and patterns of neonatal sepsis. However, the quantified contribution of a particular containment measure requires further investigation.

High non-compliance rate among presumptive tuberculosis cases referred from peripheral health facilities in silti district of Southern Ethiopia: a mixed methods study.

BACKGROUND: For presumptive Tuberculosis (TB) case referral to be effective, most of the referred cases need to present themselves to health facilities for assessment and testing. Otherwise, cases of TB could be missed, and these cases are at an increased risk of delayed diagnosis, complications and death. Further, their care incurs significantly higher costs. This study assessed referral compliance as well as factors attributable to compliance/non-compliance to referral of presumptive TB cases in Silti district, Southern Ethiopia. METHOD: We applied a mixed design involving both quantitative and qualitative methods. A randomly selected sample of 384 presumptive TB cases referred between January, 2014 and July 2021 were included in this study from the records of 12 health posts. Purposefully selected presumptive TB cases and Health Extension Workers were also interviewed to get in-depth information on the reasons for compliance and non-compliance to referral. STATA version 14 was employed to model the data using logistic regression. Qualitative data were analyzed using thematic content analysis. RESULTS: Of the 384 referred presumptive TB cases, close to 49% did not present themselves to the referral facilities. About 66% (n = 249) of the referred cases were women, and 62% (n = 119) of those who complied to referral were women. In multivariate analysis, cough [AOR = 3.4, 95%CI: 1.54-7.32], and chest pain [AOR = 2.7, 95%CI: 1.45-5.05] were independent predictors of compliance to referral. Nearly 5.5% (n = 21) of TB cases of all types were identified. The qualitative data analysis revealed that severe disease symptoms, HEW's recommendations, and social issues as reasons improving compliance while personal and social factors, financial problems, lack of awareness about TB and transportation were reasons impeding compliance to referral. CONCLUSION: Our study showed a high level of non-compliance to referral among referred presumptive TB cases. We also found that more women were referred and also complied with the referral. Strengthening community awareness about the disease symptoms and the existence of free treatment, addressing misconceptions about TB, supporting the elderly and disabled, and checkup house visits after referral could improve compliance to referral.

Traditional medicinal plants used in the treatment of tuberculosis in Ethiopia: A systematic review.

Background: Majority of people in Ethiopia heavily rely on traditional medicinal plants to treat a number of diseases including tuberculosis (TB). However, there has been lack of comprehensive evidences on taxonomic distribution of medicinal plant species, methods of preparation of remedies from these plants and how the remedies are administered. This systematic review is designed to examine and synthesize available evidences focusing on medicinal plants that have been used for TB treatment in Ethiopia. Methods: Research findings related to ethno-botanical and pharmacological approaches of TB remedies were retrieved from databases. Electronic libraries of Ethiopian Universities and relevant church-based religious books were also reviewed as additional sources. Evidences are searched and organized in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Result: From a total of 68 research documents that reported use of plants for treatment of TB 98 plants species belonging to 82 genera and 49 families were identified. The most frequently reported plant species belonged to family Lamiaceae (n = 8), Euphorbiaceae (n = 7), Cucurbitaceae (n = 6) and Fabaceae (n = 6). Croton macrostachyus, Allium sativum, and Myrsine Africana were the most often mentioned anti-TB medicinal plants. Shrubs (35.7%) and trees (29.6%) were reported as dominant growth forms while plant roots (31.6%) and leaves (28.6%) were frequently used plant parts for the preparations of the treatment. The most favored administration route was oral (59.1%). About 87% of the preparations were made from fresh plant materials. No experimental/clinical evidence was presented for 79.6%(78/98) of the reported plants to support their anti-mycobacterial activities. Conclusion: In Ethiopia, the number of herbal remedies is enormous and their use for TB treatment is a common practice. However, majority of them are not yet backed up by evidence generated through scientific experimentation and this warrants further experimental and clinical validations. Moreover, the efficacy, toxicity and safety tests should be initiated and this would help in the rapid identification of new anti-TB regimens, and possibly it would lead to developing more effective new plant-based drugs. This systematic review will serve as a reference for the selection of plants for developing new anti-TB regimens.

Stool-based Xpert MTB/RIF assay for the diagnosis of pulmonary tuberculosis in children at a teaching and referral hospital in Southwest Ethiopia.

BACKGROUND: Diagnosis of tuberculosis (TB) in children is challenging mainly due to the difficulty of obtaining respiratory specimen and lack of sensitive diagnostic tests. The objective of this study was to evaluate the diagnostic performance of Xpert MTB/RIF (Xpert here after) for the diagnosis of pulmonary TB (PTB) from stool specimen in children. METHODS: A cross-sectional study was conducted among consecutively recruited children (less than 15 years old) with presumptive PTB at Jimma Medical Center, Ethiopia. One pulmonary specimen (expectorated sputum or gastric aspirate) was collected from each participant and tested for TB by Xpert and Lowenstein-Jensen (LJ) culture. In addition, one stool specimen per child was collected and tested by Xpert after a single step, centrifuge-free stool processing method adapted from KNCV TB Foundation. Diagnostic performance of Xpert was calculated with reference to LJ culture and to a composite reference standards (CRS) comprising of confirmed TB (positive by Xpert and/or culture) and unconfirmed TB (clinical diagnosis with improvement after anti-TB treatment). RESULTS: A total of 178 children were enrolled; 152 of whom had complete microbiological results. Overall, TB was diagnosed in 13.2% (20/152) of the children with presumptive TB. Of these, only ten had microbiologically confirmed TB (positive Xpert and/or culture) and the remaining ten were clinically diagnosed with positive response to anti-TB treatment and were classified as unconfirmed TB. Stool Xpert had sensitivity of 100% (95%CI: 66.4-100) and specificity of 99.3% (95%CI: 96.2-100) compared to culture; however, the sensitivity was decreased to 50% (95%CI: 27.2-72.8) when compared to CRS. The Xpert on gastric aspirate had sensitivity of 77.8% (95%CI: 40-97.2) compared to culture and 40% (95%CI: 19.1-64) compared to CRS. CONCLUSIONS: The sensitivity of Xpert for stool sample is comparable to that for gastric aspirate. Stool sample is a potential alternative to pulmonary specimen in the diagnosis of pulmonary TB in children using Xpert.

Combination of Xpert® MTB/RIF and DetermineTM TB-LAM Ag improves the diagnosis of extrapulmonary tuberculosis at Jimma University Medical Center, Oromia, Ethiopia.

BACKGROUND: Ethiopia is one of the high burden countries for extrapulmonary tuberculosis (EPTB); however, the prompt diagnosis of EPTB remains challenging. This study is aimed to evaluate the diagnostic performance of Xpert MTB/RIF and DetermineTM TB-LAM Ag (TB-LAM) for the prompt diagnosis of EPTB in Ethiopia. METHODS: A total of 147 presumptive EPTB patients, including 23 HIV- positive participants were enrolled. Extra-pulmonary samples were collected from all presumptive EPTB cases and tested for Mycobacterium tuberculosis complex (MTBC) using fluorescent microscopy, Xpert MTB/RIF, and culture. Additionally, urine samples were also collected from 126 participants and were tested by DetermineTM TB-LAM Ag (Alere Inc, Waltham, USA). The Sensitivity and specificity of Xpert and TB- LAM tests were calculated by comparing with a composite reference standard (CRS), which comprises smear microscopy, culture and response to empirical anti-TB treatment. RESULTS: Of 147 patients, 23 (15.6%) were confirmed EPTB cases (culture-positive), 14 (9.5%) were probable EPTB (clinically, radiologically or cytologically positive and received anti-TB treatment with good response), and 110 (74.8%) were classified as "non- TB" cases. Compared to the composite reference standard (CRS), the overall sensitivity and specificity of Xpert MTB/RIF were 43.2% and 100%, respectively with the highest sensitivity for Lymph node aspirate (85.7%) and lower sensitivity for pleural fluid (14.3%) and 100% specificity for all specimen types. The sensitivity and specificity of TB-LAM were 33.3% and 94.4% respectively with the highest sensitivity for HIV co-infected participants (83.3%). The sensitivity of the combination of Xpert MTB/RIF and TB-LAM tests regardless of HIV status was 61.1% whereas the sensitivity was improved to 83.3% for HIV-positive cases. CONCLUSION: TB-LAM alone has low sensitivity for EPTB diagnosis; however, the combination of TB-LAM and Xpert MTB/RIF improves the diagnosis of EPTB particularly for countries with high EPTB and HIV cases.

Detection of Mycobacterium tuberculosis and rifampicin resistance by Xpert® MTB/RIF assay among presumptive tuberculosis cases at Jimma University Medical Center, Southwest Ethiopia.

BACKGROUND: Rapid diagnosis of tuberculosis (TB) and detection of drug resistance are very important for timely and appropriate management of patients. Xpert MTB/RIF assay is approved for use in TB and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert MTB/RIF assay under routine clinical settings with a heterogeneous group of patients and sample types in Ethiopia. METHODS: A retrospective study was carried out in 2220 presumptive TB cases at Jimma University Medical Center. Data were gathered from the registration logbook using formatted data extraction tools and double entered to epidata version 3.1 and further transported to SPSS version 20 for analysis. Associations were determined using the Chi-square test and P-value <0.05 was considered statistically significant. RESULTS: Of 2220 cases enrolled, 1665 (75%) were adults and the remaining 555 (25%) were children aged less than 14 years. The majority, 1964 (88.46%), had pulmonary manifestation and 256 (11.54%) had extrapulmonary involvements. The overall, frequency of Mycobacterium tuberculosis (MTB) was 9.3% (206/2220), among this 10.27% (171/1665) and 6.3% (35/555) were adults and children, respectively. M. tuberculosis was detected from 171 (8.75%) of pulmonary patients and 35 (13.28%) of extrapulmonary manifested patients. Out of 206 M. tuberculosis positive cases, 7(3.4%) were rifampicin-resistant: four from pulmonary tuberculosis (PTB) patients and three from EPTB patients. In the Chi-square test, the age group of 15-24 years, previous history of TB, pus/lymph node sample, and being HIV positive were significantly associated with TB positivity by Xpert MTB/RIF (P-value <0.001). CONCLUSION: These data suggest that the overall frequency of M. tuberculosis and rifampicin resistance was found to be relatively low compared to the previous reports in Ethiopia. Nevertheless, better diagnostic tools and approaches are still vital to halt the burden of TB and drug-resistant TB in the country.

The value of lateral flow urine lipoarabinomannan assay and empirical treatment in Xpert MTB/RIF ultra negative patients with presumptive TB: a prospective cohort study.

The value of Lateral Flow urine Lipoarabinomannan (LF-LAM) assay and the role of empiric tuberculosis (TB) treatment in the era of the highly sensitive Xpert MTB/RIF Ultra (Xpert Ultra) assay is unclear. This study aimed to assess the additional yield of LF-LAM assay when used in combination with Xpert Ultra, and the role of empiric TB treatment when Xpert Ultra used as the initial diagnostic in presumptive TB cases admitted to a tertiary hospital in Ethiopia. We performed a secondary analysis of a cohort of hospitalized Xpert MTB/RIF-negative patients. Sputum samples were examined for Mycobacterium tuberculosis by culture and Xpert Ultra. In HIV positive and severely ill patients, a urine sample was collected for the LF-LAM assay. Treatment outcome was assessed six months after enrollment. Logistic regression was used to identify factors predictive of deaths among Xpert Ultra negative patients. The Xpert Ultra assay diagnosed 31 of the 35 culture positive among the 250 hospitalized Xpert MTB/RIF-negative participants. The LF-LAM assay did not identify any case not detected by Xpert Ultra among the 52 (21.4%) participants living with HIV and the 16 patients with severe disease. Among Xpert Ultra negative patients, those who received empirical TB treatment had a similar odds of death (aOR 0.74, 95% CI: 0.1-2.7) as those not started on TB treatment. Low body mass index (≤ 18.5 kg/m2) was the only significant predictor of death in Xpert Ultra negative patients (aOR 4. 0, 95% CI: 1.08-14.6). In this prospective cohort, LF-LAM did not improve the diagnostic yield when used in combination with Xpert Ultra. Empiric TB treatment for Xpert Ultra negative presumptive TB cases was not associated with death at six months. Future studies in diverse settings should be to determine the optimal management of Xpert Ultra negative patients.

The role of chest radiography in the diagnosis of bacteriologically confirmed pulmonary tuberculosis in hospitalised Xpert MTB/RIF-negative patients.

The role of chest radiography to diagnose active tuberculosis in symptomatic patients who have a negative Xpert MTB/RIF (Xpert) test result is unclear. This study aimed to assess the performance of chest radiography and the value of chest radiography findings for a prediction tool to identify cases of active pulmonary tuberculosis among symptomatic, Xpert-negative hospitalised patients. Xpert-negative patients hospitalised between January and July 2019 at Jimma University Medical Center in Ethiopia were assessed by mycobacterial culture and chest radiography. Chest radiography was interpreted by a clinician for clinical decision making and by a radiologist for research purposes. Using bacteriological confirmation as the reference standard, the performance of chest radiography to diagnose active tuberculosis was assessed by the area under the receiver operating characteristic curve (AUC); predictors of active tuberculosis were identified using bivariate and multivariate logistic regression analyses. Of 247 Xpert-negative patients, 38% and 40% were classified as suggestive of tuberculosis by clinician and radiologist, respectively. Of the 39 (15.8%) bacteriologically confirmed cases, 69% and 79% were classified as having chest radiography findings suggestive of tuberculosis by clinician or radiologist, respectively. While there was a strong association between bacteriologically confirmed tuberculosis and chest radiography classified by clinician as suggestive of tuberculosis (adjusted OR 2.7, 95% CI 1.2-6.6), chest radiography with signs typical of tuberculosis (adjusted OR 5.3, 95% CI 2.1-14.4) or compatible with tuberculosis (adjusted OR 5.1, 95% CI 1.3-20.0), the positive predictive value of the chest radiography was low (27% and 34% for classification by clinician and radiologist, respectively). The addition of chest radiography findings by clinician or radiologist to clinical characteristics did not improve the performance of the prediction tool, with similar risk classification distribution, AUCs and negative and positive prediction values. Despite the strong association between chest radiography findings and active tuberculosis among hospitalised Xpert negative individuals, chest radiography findings did not improve the performance of a risk prediction tool based solely on clinical symptoms. Countries with a high tuberculosis/HIV burden should urgently replace Xpert by the more sensitive Xpert Ultra assay to improve the diagnosis of active tuberculosis.

Diagnostic implications and inpatient mortality related to tuberculosis at Jimma Medical Center, southwest Ethiopia.

BACKGROUND: Tuberculosis (TB) is one of the major public health problems in Ethiopia. Determining discharge outcome of TB cases helps to understand the effectiveness of TB diagnosis effort to improve case management. The objective of this study was to assess discharge outcomes and factors associated with death among patients on TB treatment admitted in a referral hospital in southwest Ethiopia. METHODS: A retrospective study was conducted in Jimma Medical Center by reviewing medical records of TB patients (age ≥15 years) admitted to medical wards from January 2015 to December 2017. Demographic and related data was collected using data collection format. The clinical evaluation outcome of an individual patient at discharge was recorded. Descriptive statistics were used to summarize participant characteristics. Multivariate logistic regression analyses were used to evaluate the risk factors for TB mortality. RESULTS: Among 465 patients included in the review, 225 (48.4%) were pulmonary (PTB) and 240 (51.6%) extra-pulmonary TB (EPTB) cases. Overall, 190 (40.9%) had bacteriologically confirmed for TB. HIV status was documented for 340 (73.1%) of them; 93 (27.4%) were found to be positive. The prevalence of HIV infection among EPTB and PTB cases was 50/275 (18.2%) and 43/190 (22.8%), respectively. A quarter of the patient, 114 (24.5%), died in the hospital while the rest were discharged with clinical improvement. Compared to smear positive PTB, the risk of death was two times higher in patients with smear negative PTB cases (aOR 2.3, 95% CI: 1.3-4.2). TB patients with coronary obstructive pulmonary disease (COPD) (aOR 4.6, 95% CI: 1.3-16.7), diabetes mellitus (aOR 5.7, 95% CI: 1.5-23.7), heart disease (aOR 3.8, 95% CI: 1.4-10.4) had about four-fold increased risk of death. HIV-positive patients had a higher risk of mortality (aOR 2.9, 95% CI: 1.7-5.0) than HIV-negative patients. The risk of death was not affected by the type of TB diagnosed, as 27.6% of EPTB and 31.9% PTB were died (p = 0.457). CONCLUSION: TB was associated with high inpatient mortality at Jimma Medical Center. Mortality was found to be higher among unconfirmed cases, those with COPD, diabetes mellitus, heart disease and HIV infection. Thus, any effort to curtail mortality in such high TB burden setting should focus on improving TB diagnosis and addressing major comorbid medical conditions.

Capacity building for whole genome sequencing of Mycobacterium tuberculosis and bioinformatics in high TB burden countries.

BACKGROUND: Whole genome sequencing (WGS) is increasingly used for Mycobacterium tuberculosis (Mtb) research. Countries with the highest tuberculosis (TB) burden face important challenges to integrate WGS into surveillance and research. METHODS: We assessed the global status of Mtb WGS and developed a 3-week training course coupled with long-term mentoring and WGS infrastructure building. Training focused on genome sequencing, bioinformatics and development of a locally relevant WGS research project. The aim of the long-term mentoring was to support trainees in project implementation and funding acquisition. The focus of WGS infrastructure building was on the DNA extraction process and bioinformatics. FINDINGS: Compared to their TB burden, Asia and Africa are grossly underrepresented in Mtb WGS research. Challenges faced resulted in adaptations to the training, mentoring and infrastructure building. Out-of-date laptop hardware and operating systems were overcome by using online tools and a Galaxy WGS analysis pipeline. A case studies approach created a safe atmosphere for students to formulate and defend opinions. Because quality DNA extraction is paramount for WGS, a biosafety level 3 and general laboratory skill training session were added, use of commercial DNA extraction kits was introduced and a 2-week training in a highly equipped laboratory was combined with a 1-week training in the local setting. INTERPRETATION: By developing and sharing the components of and experiences with a sequencing and bioinformatics training program, we hope to stimulate capacity building programs for Mtb WGS and empower high-burden countries to play an important role in WGS-based TB surveillance and research.

Lipid and Lipoprotein Profile in HIV-Infected and Non-Infected Diabetic Patients: A Comparative Cross-Sectional Study Design, Southwest Ethiopia.

BACKGROUND: Lipoproteins are complexes of lipids and proteins that are essential for the transport of cholesterol, triglycerides, and fat-soluble vitamins. The linkage between chronic diseases like diabetes mellitus and HIV infection increases the complication of the diseases and worsens the clinical outcome of the patients. PURPOSE: To assess and compare lipid and lipoprotein profiles among HIV-infected and non-infected diabetic patients, and to identify independent predictor variables for abnormal lipid and lipoprotein profiles. PATIENTS AND METHODS: A comparative cross-sectional study design was used to carry out the research, and a convenient sampling technique was used to include 96 adult diabetic patients (48 HIV-infected and 48 non-infected diabetics). Socio-demographic and clinical data were collected by interviewer-administered questionnaire. Five milliliter blood sample was collected and processed for lipid and lipoprotein profile measurement. Multivariate and bivariate logistic regressions were used to identify independent predictor variables for abnormal lipid and lipoprotein profiles. RESULTS: The prevalence of diabetic dyslipidemia was 41.7% and 37.5% in HIV-infected and non-infected diabetic patients, respectively. Hypercholesterolemia was more commonly detected among HIV-infected diabetic patients than non-HIV-infected, 25.0% versus 18.8%, respectively. Similarly, hypertriglyceridemia was more commonly observed in HIV-infected (31.3%) than non-infected diabetic patients (20.8%). About 25.0% HIV-infected diabetic patients had combined hyperlipidemia (hypercholesterolemia plus hypertriglyceridemia); and about 4.2% had hypoalphalipoproteinemia or isolated low HDL-C. Being female and long duration of diabetes mellitus were independent predictor variables for abnormal lipid and lipoprotein profiles in HIV-infected patients. Similarly, being female and high blood pressure were independent predictor variables in non-HIV-infected diabetic patients. CONCLUSION: High prevalence lipid and lipoprotein abnormalities were detected in HIV-infected diabetic patients even though the abnormalities were also common in non-HIV co-morbid diabetic patients. Hence, proactive screening and treatment of blood glucose, lipid, and lipoprotein abnormalities are critically important and should be part of comprehensive HIV care.

Fluorescence microscopy for the diagnosis of smear-negative pulmonary tuberculosis in Ethiopia.

BACKGROUND: Despite its low sensitivity, microscopy remains the main method for the diagnosis of pulmonary tuberculosis in most laboratories in Ethiopia. Few studies have evaluated the performance of light-emitting diode fluorescent microscopy (LED-FM) in bleach-concentrated smear-negative sputum specimens. OBJECTIVE: This study aimed to evaluate the diagnostic performance of LED-FM for smear-negative pulmonary tuberculosis in Ethiopia. METHODS: A total of 194 adult patients with a cough lasting for more than two weeks, and who had three direct smear-negative sputum tests for Mycobacterium tuberculosis by Ziehl-Neelsen light microscopy, were included. All direct Ziehl-Neelsen-stained smear-negative sputum samples were cultured and were also visualised by LED-FM. Smears for LED-FM were performed from bleach-concentrated sputum sediment. The diagnostic performance of the LED-FM was compared to the culture method (the reference standard). RESULTS: Of the 194 smear-negative sputum specimens analysed, 28 (14.4%) were culture-positive and 21 (10.8%) were LED-FM-positive for M. tuberculosis. However, only 11 of the 21 (52.4%) LED-FM-positive patients had a confirmed tuberculosis diagnosis by culture. Light-emitting diode fluorescence microscopy (FM) had a sensitivity of 39.3% (95% confidence interval: 21.2-57.4) and specificity of 93.9% (95% confidence interval: 90.4-97.6). Ten LED-FM-positive specimens were culture-negative, and all of these specimens had scanty grading (1-19 bacilli per 40 fields on LED-FM). CONCLUSION: This study showed that implementation of LED-FM on bleach pre-treated and concentrated sputum can significantly improve the diagnosis of smear-negative pulmonary tuberculosis. However, all scanty grade, positive smears by LED-FM need to be confirmed by reference culture method.

Role of empiric treatment in hospitalized patients with Xpert MTB/RIF-negative presumptive pulmonary tuberculosis: A prospective cohort study.

OBJECTIVES: The ability of clinical algorithms to identify tuberculosis disease and the impact of empiric treatment on survival in people with a negative Xpert MTB/RIF (Xpert) result remains poorly documented. METHODS: Hospitalized Xpert-negative patients (125 initiated on empiric tuberculosis treatment based on a clinical algorithm and 125 in whom tuberculosis treatment was not started) were enrolled. Sputum samples were evaluated for Mycobacterium tuberculosis by culture. All study participants were followed up for 6 months. RESULTS: Xpert-negative inpatients in whom empiric tuberculosis treatment was initiated were more likely to have microbiological confirmed tuberculosis compared to those in whom empiric tuberculosis treatment was not started (24.8% vs 6.4%, p=0.0001). Six-month risk of death was 5.2%, but the risk was twice as high in people with bacteriological confirmation of TB (10.3% vs 4.3%, p=0.12). Cardinal symptoms of TB were associated with bacteriological confirmation and a decision to start empiric treatment. The positive predictive value of the clinical algorithm was 24.8% and empiric treatment did not affect 6-month risk of death (5.6% vs 4.8%, p=0.78). CONCLUSIONS: Clinical algorithm identifies the majority of confirmed tuberculosis cases among Xpert-negative inpatients. Empiric treatment did not impact survival and resulted in substantial overtreatment. The more sensitive Xpert Ultra assay should be used to eliminate the need for empiric tuberculosis treatment.

Dyslipidemia and associated factors among women using hormonal contraceptives in Harar town, Eastern Ethiopia.

OBJECTIVE: Dyslipidemia is abnormal amount of lipid in blood. Hormonal contraceptives affect lipid metabolism and can enhance the risk of vascular disease like atherosclerosis. In Harar, among contraceptive users, biochemical changes follow up is almost none and magnitude of dyslipidemia is not known. Therefore this study is designed to determine prevalence of dyslipidemia and its predisposing factors. Accordingly, cross-sectional study was conducted from April to June 2014 among hormonal contraceptive users from three health centers and one hospital. Socio-demographic data, anthropometric measurements, and blood biochemical tests were performed for every participant. Descriptive statistics and logistic regression analysis with 95% confidence interval using SPSS was used. RESULT: Totally 365 participants were included and the prevalence of dyslipidemia was 34.8%. The mean levels ± standard deviation of total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), the total cholesterol to HDL ratio, and triglyceride were 186 ± 27 mg/dl, 121 ± 31 mg/dl, 45.21 ± 7.7 mg/dl, 4.44, and 108 ± 3.45 mg/dl, respectively. Age, fasting blood sugar, drinking coffee twice and eating no vegetables 4 times/week were identified as predictors of dyslipidemia. In conclusion, hormonal contraceptive users of Harar have high rate of dyslipidemia. This result emphasizes the urgent need for a public health strategy for prevention, early detection, and treatment of dyslipidemia.